1. Field of the Invention
This invention relates to a physiologically active polypeptide, a DNA encoding the polypeptide, and a pharmaceutical composition for treating and curing circulation diseases comprising the polypeptide as an effective ingredient.
2. Description of the Background Art
Structures of new polypeptides secreted by human or rat atrium and having natriuretic activity have successively been determined and reported in the years 1983–1884 [Biochem. Biophys. Res. Commun. 117, 859 (1983); Biochem. Biophys. Res. Commun. 118, 131–139 (1984)]. These polypeptides were named artium natriuretic peptides (hereinafter referred to as “ANP”). Since they have strong natriuretic activity as well as relaxing activity of vessel and smooth muscle, they are attracting much attention as a new peptide medicine for circulation disease.
In 1988, a new peptide having diuretic activity was isolated in a purified form from porcine brain. Its structure was determined and the peptide was named “porcine brain natriuretic peptide” (hereinafter referred to as porcine BNP or pBNP) [Nature, 332, No. 6159, 78–81 (1988); Biochem. Biophys. Res. Commun. 155, 726–732 (1988)]. Pharmaceutical activities of pBNP resemble those of ANP, and include diuretic activity, natriuretic activity, vasodepressor activity, chicken rectum relaxation activity, and the like. The specific activities of pBNP also resemble those of ANP, except that the rectum relaxation activity of pBNP is 3 to 4 times higher than that of ANP. This is the reason that pBNP is expected to be a new medicine for circulation disease and that studies involving DNA of porcine BNP are being undertaken. Cloning of cDNA possessing a base sequence encoding porcine BNP and its precursor has been reported [Biochem. Biophys. Res. Commun. 157 (1), 410–416 (1988)].
Development of brain natriuretic peptide derived from human being (hereinafter referred to as human BNP or hBNP) has been desired as a therapeutic agent for human circulation diseases. Such a peptide, however, has not been heretofore found. Nor has its structure been clarified neither on a DNA level nor on a peptide or protein level.
In view of this situation, the present inventors have conducted extensive studies to obtain human BNP, and have been successful in cloning cDNA encoding human BNP by screening a cDNA library.
Furthermore, the present inventors have synthesized various human BNPs based on the amino acid sequence deduced from the cDNA base sequence and have studied their pharmacological activities. As a result, the inventors have found that these BNPs had excellent smooth muscle relaxation and natriuretic activities.